Dehydroepiandrosterone supplementation appears to have some benefit in patients with primary adrenal insufficiency. But it does not change fat mass, improve cognitive or sexual function, or necessarily alleviate physical fatigue, according to a 12-month placebo-controlled trial involving 100 patients.
Dehydroepiandrosterone (DHEA) therapy does improve lean body mass, some aspects of well-being, and bone mineral density at the femoral neck, investigators reported.
The findings support a previous study they conducted, which found DHEA improved patients' sense of well-being, said Dr. Eleanor M. Gurnell of the department of medicine, Addenbrooke's Hospital, Cambridge, England, and colleagues (J. Clin. Endocrinol. Metab. 2008;93:400–9).
They assumed the well-being finding would hold up, and designed the current study to be large enough to provide statistically significant data on whether long-term supplementation would prevent bone density loss, which most Addison's patients experience and which does not improve with glucocorticoid and mineralocorticoid treatment.
Of 106 patients (62 women) with primary adrenal insufficiency, 100 took DHEA (50 mg daily) or placebo for the full 12 months. The median age of the subjects was 46 years, their median duration of having Addison's was 10–11 years.
Serum DHEA levels monitored during the study indicated good compliance by those taking active drug, and raised DHEA levels from decidedly below normal to within the physiologic range for a young adult.
At the outset, bone mineral density was low in the subjects, with about 39% of the men and women having density T scores indicative of osteopenia in the lumbar spine and femoral neck. After 12 months of treatment, the placebo group had a continued mean loss in both the spine and femoral neck. The treated group, however, had a mean gain in the femoral neck (0.004 g/cm
The treatment did not produce any different changes in body mass index, though it improved total lean body mass and relative truncal lean mass. It did not change fat mass.
Cognitive function measures using the National Adult Reading Test showed no improvement relative to placebo, even when a subanalysis only looked at patients aged over 45 years. Psychological status of the study subjects was measured using three instruments, the Short Form-36, the General Health Questionnaire-30, and the Multidimensional Fatigue Inventory-20. Overall, the study subjects had scores that were worse than those of the general population at baseline, and scores generally improved with DHEA treatment when the subjects were tested again at 12 months. They declined after a 1-month drug washout period at the end of the study.
But only two parameters of psychological status showed a mean improvement that was statistically significant relative to placebo. One was the role-emotional dimension of health on the Short Form-36 when measured at 12 months, and the other was the mental fatigue portion of the Multidimensional Fatigue Inventory-20 when measured at 6 months. By 12 months, there was no significant difference in the mental fatigue portion, however.
The fact that the study documented improvement in psychological status with DHEA treatment, together with a decline when treatment had been stopped for a month, indicated that there probably was some definite improvement, even if it was not statistically significant.
One of the largest differences seen in a psychological parameter at the beginning of the study was in the self-esteem component, a pattern that has been documented in other studies. It suggests there may be a specific psychological abnormality profile associated with Addison's disease.
Regarding side effects, 64% of 31 women on DHEA developed skin spots, 45% noted greasy skin, and 58% reported an increase in axillary hair. There were no observed changes in libido or sexual function in either gender.
The study was supported financially by the National Osteoporosis Society, National Institute for Health Research Biomedical Research Centre, and Wellcome Trust.